Z-Guggulsterone attenuates astrocytes-mediated neuroinflammation after ischemia by inhibiting toll-like receptor 4 pathway.
J Neurochem
; 147(6): 803-815, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30168601
ABSTRACT
Inflammatory damage plays a pivotal role in ischemic stroke pathogenesis and may represent one of the therapeutic targets. Z-Guggulsterone (Z-GS), an active component derived from myrrh, has been used to treat various diseases. The traditional uses suggest that myrrh is a good candidate for anti-inflammatory damage. This study was to investigate the anti-inflammatory and neuroprotective effects of Z-GS following cerebral ischemic injury, as well as the exact mechanisms behind them. Rat middle cerebral artery occlusion (MCAO) model and in vitro astrocytes oxygen-glucose deprivation (OGD) model were adopted to simulate ischemic stroke. Z-GS (30 or 60 mg/kg) was administered intraperitoneally immediately after reperfusion, while astrocytes were maintained in 30 or 60 µM Z-GS before OGD treatment. The results indicated that Z-GS significantly alleviated neurological deficits, infarct volume and histopathological damage in vivo, and increased the astrocytes viability in vitro. Moreover, the treatment of Z-GS inhibited the astrocytes activation and down-regulated the mRNA levels of pro-inflammatory cytokines. Furthermore, the activated TLR4-NF-κB signaling pathways induced by MCAO or OGD were significantly suppressed by Z-GS treatment, which was achieved via inhibiting the phosphorylation of JNK. Our results demonstrated that Z-GS exerted neuroprotective and anti-inflammatory properties through preventing activation of TLR4-mediated pathway in the activated astrocytes after ischemia injury. Therefore, Z-GS could be considered as a promising candidate for the treatment of ischemic stroke.
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MEDLINE
Assunto principal:
Pregnenodionas
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Isquemia Encefálica
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Astrócitos
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Fármacos Neuroprotetores
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Receptor 4 Toll-Like
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Inflamação
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article